tbuckley/cabot-search huggingface dataset:
Countrywide multi-serotype outbreak of Salmonella Bovismorbificans ST142 and monophasic Salmonella Typhimurium ST34 associated with dried pork sausages in France, September 2020* to January 2021
Authors: Maria Pardos de la Gandara, Nelly Fournet, Laetitia Bonifait, Sophie Lefèvre, Marianne Chemaly, Charlotte Grastilleur, Sabrina Cadel-Six, Patrick Fach, Agnès Pignault, Anne Brisabois, Nathalie Jourdan-Da Silva, François-Xavier Weill
Journal: Eurosurveillance (2023)

The French National Reference Centre for Escherichia coli, Shigella and Salmonella (FNRC-ESS) detected two human clusters of 33 cases (median age: 10 years; 17 females) infected by Salmonella enterica serotype Bovismorbificans, ST142, HC5_243255 (EnteroBase HierCC‑cgMLST scheme) in September-November 2020 and of 11 cases (median age: 11 years; seven males) infected by S. enterica serotype 4,12:i:-, ST34, HC5_198125 in October-December 2020. Epidemiological investigations conducted by Santé publique France linked these outbreaks to the consumption of dried pork sausages from the same manufacturer. S. Bovismorbificans and S. 4,12:i:- were isolated by the National Reference Laboratory from different food samples, but both strains were identified in a single food sample only by qPCR. Three recalls and withdrawals of dried pork products were issued by the French general directorate of food of the French ministry for agriculture and food in November 2020, affecting eight supermarket chains. A notification on the European Rapid Alert System for Food and Feed and a European urgent enquiry on the Epidemic Intelligence Information System for Food and Waterborne Diseases and Zoonoses (EPIS-FWD) were launched. No cases were reported outside France. Outbreaks caused by multiple serotypes of Salmonella may go undetected by protocols in standard procedures in microbiology laboratories.
Dynamic chromatin regulatory programs during embryogenesis of hexaploid wheat
Authors: Long Zhao, Yiman Yang, Jinchao Chen, Xuelei Lin, Hao Zhang, Hao Wang, Hongzhe Wang, Xiaomin Bie, Jiafu Jiang, Xiaoqi Feng, Xiangdong Fu, Xiansheng Zhang, Zhuo Du, Jun Xiao
Journal: Genome biology (2023)

Abstract Background Plant and animal embryogenesis have conserved and distinct features. Cell fate transitions occur during embryogenesis in both plants and animals. The epigenomic processes regulating plant embryogenesis remain largely elusive. Results Here, we elucidate chromatin and transcriptomic dynamics during embryogenesis of the most cultivated crop, hexaploid wheat. Time-series analysis reveals stage-specific and proximal–distal distinct chromatin accessibility and dynamics concordant with transcriptome changes. Following fertilization, the remodeling kinetics of H3K4me3, H3K27ac, and H3K27me3 differ from that in mammals, highlighting considerable species-specific epigenomic dynamics during zygotic genome activation. Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 deposition is important for embryo establishment. Later H3K27ac, H3K27me3, and chromatin accessibility undergo dramatic remodeling to establish a permissive chromatin environment facilitating the access of transcription factors to cis -elements for fate patterning. Embryonic maturation is characterized by increasing H3K27me3 and decreasing chromatin accessibility, which likely participates in restricting totipotency while preventing extensive organogenesis. Finally, epigenomic signatures are correlated with biased expression among homeolog triads and divergent expression after polyploidization, revealing an epigenomic contributor to subgenome diversification in an allohexaploid genome. Conclusions Collectively, we present an invaluable resource for comparative and mechanistic analysis of the epigenomic regulation of crop embryogenesis.
Short-chain fatty acid production in accessible and inaccessible body pools as assessed by novel stable tracer pulse approach is reduced by aging independent of presence of COPD
Authors: Sarah K Kirschner, Parisa Ghane, Jaekwan K Park, Sunday Y Simbo, Ivan Ivanov, Ulisses M Braga-Neto, Gabriëlla A M Ten Have, John J Thaden, Mariëlle P K J Engelen, Nicolaas E P Deutz
Journal: Metabolism (2023)
Discovery of associative patterns between workplace sound level and physiological wellbeing using wearable devices and empirical Bayes modeling
Authors: Karthik Srinivasan, Faiz Currim, Casey M. Lindberg, Javad Razjouyan, Brian Gilligan, Hyoki Lee, Kelli J. Canada, Nicole Goebel, Matthias R. Mehl, Melissa M. Lunden, Judith Heerwagen, Bijan Najafi, Esther M. Sternberg, Kevin Kampschroer, Sudha Ram
Journal: npj Digital Medicine (2023)

We conducted a field study using multiple wearable devices on 231 federal office workers to assess the impact of the indoor environment on individual wellbeing. Past research has established that the workplace environment is closely tied to an individual's wellbeing. Since sound is the most-reported environmental factor causing stress and discomfort, we focus on quantifying its association with physiological wellbeing. Physiological wellbeing is represented as a latent variable in an empirical Bayes model with heart rate variability measures-SDNN and normalized-HF as the observed outcomes and with exogenous factors including sound level as inputs. We find that an individual's physiological wellbeing is optimal when sound level in the workplace is at 50 dBA. At lower (<50dBA) and higher (>50dBA) amplitude ranges, a 10 dBA increase in sound level is related to a 5.4% increase and 1.9% decrease in physiological wellbeing respectively. Age, body-mass-index, high blood pressure, anxiety, and computer use intensive work are person-level factors contributing to heterogeneity in the sound-wellbeing association.
The foundation and architecture of precision medicine in neurology and psychiatry
Authors: Harald Hampel, Peng Gao, Jeffrey Cummings, Nicola Toschi, Paul M. Thompson, Yan Hu, Min Cho, Andrea Vergallo
Journal: Trends in Neurosciences (2023)

Neurological and psychiatric diseases have high degrees of genetic and pathophysiological heterogeneity, irrespective of clinical manifestations. Traditional medical paradigms have focused on late-stage syndromic aspects of these diseases, with little consideration of the underlying biology. Advances in disease modeling and methodological design have paved the way for the development of precision medicine (PM), an established concept in oncology with growing attention from other medical specialties. We propose a PM architecture for central nervous system diseases built on four converging pillars: multimodal biomarkers, systems medicine, digital health technologies, and data science. We discuss Alzheimer's disease (AD), an area of significant unmet medical need, as a case-in-point for the proposed framework. AD can be seen as one of the most advanced PM-oriented disease models and as a compelling catalyzer towards PM-oriented neuroscience drug development and advanced healthcare practice.
Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe
Authors: Gaspard Kerner, Anna-Lena Neehus, Quentin Philippot, Jonathan Bohlen, Darawan Rinchai, Nacim Kerrouche, Anne Puel, Shen-Ying Zhang, Stéphanie Boisson-Dupuis, Laurent Abel, Jean-Laurent Casanova, Etienne Patin, Guillaume Laval, Lluis Quintana-Murci
Journal: Cell Genomics (2023)

Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day inflammatory disease risk. Here, we use an ancestry-aware approximate Bayesian computation framework to estimate the nature, strength, and time of onset of selection acting on 2,879 ancient and modern European genomes from the last 10,000 years. We found that the bulk of genetic adaptation occurred after the start of the Bronze Age, <4,500 years ago, and was enriched in genes relating to host-pathogen interactions. Furthermore, we detected directional selection acting on specific leukocytic lineages and experimentally demonstrated that the strongest negatively selected candidate variant in immunity genes, lipopolysaccharide-binding protein (
Multivalent Lactobionic Acid and N‐Acetylgalactosamine‐Conjugated Peptide Nucleic Acids for Efficient In Vivo Targeting of Hepatocytes
Authors: Vikas Kumar, Aniket Wahane, Anisha Gupta, José E. Manautou, Raman Bahal
Journal: Advanced Healthcare Materials (2023)

Abstract Peptide nucleic acids (PNAs) are used/applied in various studies to target genomic DNA and RNA to modulate gene expression. Non‐specific targeting and rapid elimination always remain a challenge for PNA‐based applications. Here, the synthesis, characterization, in vitro and in vivo study of di lactobionic acid (diLBA) and tris N‐acetyl galactosamine (tGalNAc) conjugated PNAs for liver‐targeted delivery are reported. For proof of concept, diLBA, and tGalNAc conjugated PNAs (anti‐miR‐122 PNAs) were synthesized to target microRNA‐122 (miR‐122) which is over‐expressed in the hepatic tissue. Different lengths of anti‐miR‐122 PNAs conjugated with diLBA and tGalNAc are tested. Cell culture and in vivo analyses to determine biodistribution, efficacy, and toxicity profile are performed. This work indicates that diLBA conjugates show significant retention in hepatocytes in addition to tGalNAc conjugates after in vivo delivery. Full‐length PNA conjugates show significant downregulation of miR‐122 levels and subsequent de‐repression of its downstream targets with no evidence of toxicity. The results provide a robust framework for ligand‐conjugated delivery systems for PNAs that can be explored for broader biomedical applications.
Machine learning dissection of human accelerated regions in primate neurodevelopment
Authors: Sean Whalen, Fumitaka Inoue, Hane Ryu, Tyler Fair, Eirene Markenscoff-Papadimitriou, Kathleen Keough, Martin Kircher, Beth Martin, Beatriz Alvarado, Orry Elor, Dianne Laboy Cintron, Alex Williams, Md. Abul Hassan Samee, Sean Thomas, Robert Krencik, Erik M. Ullian, Arnold Kriegstein, John L. Rubenstein, Jay Shendure, Alex A. Pollen, Nadav Ahituv, Katherine S. Pollard
Journal: Neuron (2023)

Using machine learning (ML), we interrogated the function of all human-chimpanzee variants in 2,645 human accelerated regions (HARs), finding 43% of HARs have variants with large opposing effects on chromatin state and 14% on neurodevelopmental enhancer activity. This pattern, consistent with compensatory evolution, was confirmed using massively parallel reporter assays in chimpanzee and human neural progenitor cells. The species-specific enhancer activity of HARs was accurately predicted from the presence and absence of transcription factor footprints in each species. Despite these striking cis effects, activity of a given HAR sequence was nearly identical in human and chimpanzee cells. This suggests that HARs did not evolve to compensate for changes in the trans environment but instead altered their ability to bind factors present in both species. Thus, ML prioritized variants with functional effects on human neurodevelopment and revealed an unexpected reason why HARs may have evolved so rapidly.
Evaluation of Inequities in Cancer Treatment Delay or Discontinuation Following SARS-CoV-2 Infection
Authors: Adana A. M. Llanos, Adiba Ashrafi, Nabarun Ghosh, Jennifer Tsui, Yong Lin, Angela J. Fong, Shridar Ganesan, Carolyn J. Heckman
Journal: JAMA Network Open (2023)

Importance There is a disproportionately greater burden of COVID-19 among Hispanic and non-Hispanic Black individuals, who also experience poorer cancer outcomes. Understanding individual-level and area-level factors contributing to inequities at the intersection of COVID-19 and cancer is critical. Objective To evaluate associations of individual-level and area-level social determinants of health (SDOH) with delayed or discontinued cancer treatment following SARS-CoV-2 infection. Design, Setting, and Participants This retrospective, registry-based cohort study used data from 4768 patients receiving cancer care who had positive test results for SARS-CoV-2 and were enrolled in the American Society for Clinical Oncology COVID-19 Registry. Data were collected from April 1, 2020, to September 26, 2022. Exposures Race and ethnicity, sex, age, and area-level SDOH based on zip codes of residence at the time of cancer diagnosis. Main Outcomes and Measures Delayed (≥14 days) or discontinued cancer treatment (any cancer treatment, surgery, pharmacotherapy, or radiotherapy) and time (in days) to restart pharmacotherapy. Results A total of 4768 patients (2756 women [57.8%]; 1558 [32.7%] aged ≥70 years at diagnosis) were included in the analysis. There were 630 Hispanic (13.2%), 196 non-Hispanic Asian American or Pacific Islander (4.1%), 568 non-Hispanic Black (11.9%), and 3173 non-Hispanic White individuals (66.5%). Compared with non-Hispanic White individuals, Hispanic and non-Hispanic Black individuals were more likely to experience a delay of at least 14 days or discontinuation of any treatment and drug-based treatment; only estimates for non-Hispanic Black individuals were statistically significant, with correction for multiple comparisons (risk ratios [RRs], 1.35 [95% CI, 1.22-1.49] and 1.37 [95% CI, 1.23-1.52], respectively). Area-level SDOH (eg, geography, proportion of residents without health insurance or with only a high school education, lower median household income) were associated with delayed or discontinued treatment. In multivariable Cox proportinal hazards regression models, estimates suggested that Hispanic (hazard ratio [HR], 0.87 [95% CI, 0.71-1.05]), non-Hispanic Asian American or Pacific Islander (HR, 0.79 [95% CI, 0.46-1.35]), and non-Hispanic Black individuals (HR, 0.81 [95% CI, 0.67-0.97]) experienced longer delays to restarting pharmacotherapy compared with non-Hispanic White individuals. Conclusions and Relevance The findings of this cohort study suggest that race and ethnicity and area-level SDOH were associated with delayed or discontinued cancer treatment and longer delays to the restart of drug-based therapies following SARS-CoV-2 infection. Such treatment delays could exacerbate persistent cancer survival inequities in the United States.
Association of Wildfire Air Pollution With Clinic Visits for Psoriasis
Authors: Raj P. Fadadu, Marcus Green, Barbara Grimes, Nicholas P. Jewell, Divya Seth, Jason Vargo, Maria L. Wei
Journal: JAMA Network Open (2023)

This cross-sectional study examines whether clinic visits and online search interest for psoriasis were associated with wildfire air pollution after a delayed lag period.
New Life of Topoisomerase I Inhibitors as Antibody–Drug Conjugate Warheads
Authors: Yves Pommier, Anish Thomas
Journal: Clinical Cancer Research (2023)

Summary Antibody–drug conjugates (ADC) allow the delivery of cytotoxic chemotherapeutic agents to tumors. Two ADC delivering topoisomerase I (TOP1) poisons (Enhertu and Trodelvy) have recently been FDA-approved for Her2- and Trop2-expressing solid tumors. In a recent study, a TOP1-anti B7-H4 ADC was described and shown to be synergistic with a novel PARP1-selective inhibitor. See related article by Kinneer et al., p. 1086
Pellino-1 promotes intrinsic activation of skin-resident IL-17A–producing T cells in psoriasis
Authors: Sung Hee Kim, Jongwook Oh, Won Seok Roh, Jeyun Park, Kyung Bae Chung, Gwang Hee Lee, Youn Sook Lee, Jong Hoon Kim, Heung Kyu Lee, Ho Lee, Chang-Ook Park, Do-Young Kim, Min-Geol Lee, Tae-Gyun Kim
Journal: Journal of Allergy and Clinical Immunology (2023)
Transcriptomic Changes toward Osteogenic Differentiation of Mesenchymal Stem Cells on 3D‐Printed GelMA/CNC Hydrogel under Pulsatile Pressure Environment
Authors: Keya Ganguly, Sayan Deb Dutta, Aayushi Randhawa, Dinesh K. Patel, Tejal V. Patil, Ki‐Taek Lim
Journal: Advanced Healthcare Materials (2023)

Abstract Biomimetic soft hydrogels used in bone tissue engineering frequently produce unsatisfactory outcomes. Here, it is investigated how human bone‐marrow‐derived mesenchymal stem cells (hBMSCs) differentiated into early osteoblasts on remarkably soft 3D hydrogel (70 ± 0.00049 Pa). Specifically, hBMSCs seeded onto cellulose nanocrystals incorporated methacrylate gelatin hydrogels are subjected to pulsatile pressure stimulation (PPS) of 5–20 kPa for 7 days. The PPS stimulates cellular processes such as mechanotransduction, cytoskeletal distribution, prohibition of oxidative stress, calcium homeostasis, osteogenic marker gene expression, and osteo‐specific cytokine secretions in hBMSCs on soft substrates. The involvement of Piezo 1 is the main ion channel involved in mechanotransduction. Additionally, RNA‐sequencing results reveal differential gene expression concerning osteogenic differentiation, bone mineralization, ion channel activity, and focal adhesion. These findings suggest a practical and highly scalable method for promoting stem cell commitment to osteogenesis on soft matrices for clinical reconstruction.
Trends in the Prevalence and Treatment of Diabetic Macular Edema and Vision-Threatening Diabetic Retinopathy Among Commercially Insured Adults Aged &amp;lt;65 Years
Authors: Elizabeth A. Lundeen, Minchul Kim, David B. Rein, John S. Wittenborn, Jinan Saaddine, Joshua R. Ehrlich, Christopher S. Holliday
Journal: Diabetes Care (2023)

OBJECTIVE Examine the 10-year trend in the prevalence and treatment of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) among commercially insured adults with diabetes. RESEARCH DESIGN AND METHODS We analyzed the 10-year trend (2009–2018) in health care claims for adults aged 18–64 years using the IBM MarketScan Database, a national convenience sample of employer-sponsored health insurance. We included patients continuously enrolled in commercial fee-for-service health insurance for 24 months who had a diabetes ICD-9/10-CM code on one or more inpatient or two or more different-day outpatient claims in the index year or previous calendar year. We used diagnosis and procedure codes to calculate the annual prevalence of patients with one or more claims for 1) any DME, 2) either DME or VTDR, and 3) antivascular endothelial growth factor (anti-VEGF) injections and laser photocoagulation treatment, stratified by any DME, VTDR with DME, and VTDR without DME. We calculated the average annual percent change (AAPC). RESULTS From 2009 to 2018, there was an increase in the annual prevalence of patients with DME or VTDR (2.1% to 3.4%; AAPC 7.5%; P &amp;lt; 0.001) and any DME (0.7% to 2.6%; AAPC 19.8%; P &amp;lt; 0.001). There were sex differences in the annual prevalence of DME or VTDR and any DME, with men having a higher prevalence than women. Annual claims for anti-VEGF injections increased among patients with any DME (327%) and VTDR with DME (206%); laser photocoagulation decreased among patients with any DME (−68%), VTDR with DME (−54%), and VTDR without DME (−62%). CONCLUSIONS Annual claims for DME or VTDR and anti-VEGF injections increased whereas those for laser photocoagulation decreased among commercially insured adults with diabetes.
RET-MAP: An International Multicenter Study on Clinicobiologic Features and Treatment Response in Patients With Lung Cancer Harboring a RET Fusion
Authors: Mihaela Aldea, Arianna Marinello, Michael Duruisseaux, Wael Zrafi, Nicole Conci, Giacomo Massa, Giulio Metro, Isabelle Monnet, Patricia Gomez Iranzo, Fabrizio Tabbo, Emilio Bria, Florian Guisier, Damien Vasseur, Colin R. Lindsay, Santiago Ponce-Aix, Sophie Cousin, Fabrizio Citarella, Vincent Fallet, Jose Nicolas Minatta, Anna Eisert, Hortense de Saint Basile, Clarisse Audigier-Valette, Laura Mezquita, Antonio Calles, Giannis Mountzios, Marco Tagliamento, Jordi Remon Masip, Judith Raimbourg, Safae Terrisse, Alessandro Russo, Diego Cortinovis, Philippe Rochigneux, David James Pinato, Alessio Cortellini, Camille Leonce, Anas Gazzah, Maria-Rosa Ghigna, Roberto Ferrara, Filippo Gustavo Dall’Olio, Francesco Passiglia, Vienna Ludovini, Fabrice Barlesi, Enriqueta Felip, David Planchard, Benjamin Besse
Journal: Journal of Thoracic Oncology (2023)

Nearly 1% to 2% of NSCLCs harbor RET fusions. Characterization of this rare population is still incomplete.This retrospective multicenter study included patients with any-stage RET positive (RET+) NSCLC from 31 cancer centers. Molecular profiling included DNA/RNA sequencing or fluorescence in situ hybridization analyses. Clinicobiological features and treatment outcomes (per investigator) with surgery, chemotherapy (CT), immune checkpoint blockers (ICBs), CT-ICB, multityrosine kinase inhibitors, and RET inhibitors (RETis) were evaluated.For 218 patients included between February 2012 and April 2022, median age was 63 years, 56% were females, 93% had adenocarcinoma, and 41% were smokers. The most frequent fusion partner was KIF5B (72%). Median tumor mutational burden was 2.5 (range: 1-4) mutations per megabase, and median programmed death-ligand 1 expression was 10% (range: 0%-55%). The most common metastatic sites were the lung (50%), bone (43%), and pleura (40%). Central nervous system metastases were found at diagnosis of advanced NSCLC in 21% of the patients and at last follow-up or death in 31%. Overall response rate and median progression-free survival were 55% and 8.7 months with platinum doublet, 26% and 3.6 months with single-agent CT, 46% and 9.6 months with CT-ICB, 23% and 3.1 months with ICB, 37% and 3 months with multityrosine kinase inhibitor, and 76% and 16.2 months with RETi, respectively. Median overall survival was longer in patients treated with RETi versus no RETi (50.6 mo [37.7-72.1] versus 16.3 mo [12.7-28.8], p < 0.0001).Patients with RET+ NSCLC have mainly thoracic and bone disease and low tumor mutational burden and programmed death-ligand 1 expression. RETi markedly improved survival, whereas ICB may be active in selected patients.
Camrelizumab Plus Carboplatin and Pemetrexed as First-Line Treatment for Advanced Nonsquamous NSCLC: Extended Follow-Up of CameL Phase 3 Trial
Authors: Caicun Zhou, Gongyan Chen, Yunchao Huang, Jianying Zhou, LiZhu Lin, Jifeng Feng, Zhehai Wang, Yongqian Shu, Jianhua Shi, Yi Hu, QiMing Wang, Ying Cheng, Fengying Wu, Jianhua Chen, Xiaoyan Lin, Yongsheng Wang, Jianan Huang, Jiuwei Cui, Lejie Cao, Yunpeng Liu, Yiping Zhang, Yueyin Pan, Jun Zhao, LiPing Wang, Jianhua Chang, Qun Chen, Xiubao Ren, Wei Zhang, Yun Fan, Zhiyong He, Jian Fang, Kangsheng Gu, XiaoRong Dong, Faguang Jin, Hongjun Gao, Guangyu An, Cuimin Ding, Xiaodong Jiang, Jianping Xiong, Xiangdong Zhou, Sheng Hu, Ping Lu, Anwen Liu, Shuliang Guo, Jianjin Huang, Chengchu Zhu, Jian Zhao, Beili Gao, Yinglan Chen, Chengping Hu, Jian Zhang, Hongmei Zhang, Hui Zhao, Yanfei Tai, Xinjing Ma, Wei Shi
Journal: Journal of Thoracic Oncology (2023)
When I use a word . . . . Medical anniversaries in 2023: <i>The Lancet</i>
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

The UK medical journal <i>The Lancet</i>, established by Thomas Wakley was first published on 5 October 1823 and weekly thereafter. Under his editorship the journal included an eclectic range of topics from both the sciences and arts, including political commentaries, reviews of plays, case reports (particularly reports of events in cases seen in various hospitals), editorials, brief commentaries on pathology and treatments (including quack medicines), extracts from newspapers, comments on various medical societies, and even chess problems. Verbatim accounts of lectures were a major feature and drew criticism from members of the medical establishment. This culminated in an attempt to obtain from the Lord Chancellor, Lord Eldon, an injunction on their publication by the surgeon John Abernethy, which was initially successful and later dissolved. During its first 10 years of publication Wakley defended 10 actions, six of which were for alleged libel, with total claims of damages to the tune of £8000, and awards amounting to £155 and a farthing. However, the journal survived the vicissitudes occasioned by his reforming zeal.